The spectrum of T helper cell (Th) defects observed in the peripheral blood leukocytes (PBL) of asymptomatic HIV-seropositive (HIV+) individuals has now been found to be predictive for the time to AIDS diagnosis and time to death. The spectrum of Th defects appears to be attributable to a reversal from a predominance of Type 1 over Type 2 function to a predominance of Type 2 over Type 1 function. Thus, it may be that Type 1 function is protective whereas Type 2 is not. The numbers of individuals and of cohorts of individuals who exhibit potent Th activity against HIV antigens, but who are seronegative continue to grow and expand. At present, among HIV-exposed but seronegative individuals the percent of HIV-specific Th responsive individuals are: gay men, 63%; intravenous drug users, 45%; accidentally-exposed health care workers, 75%; and newborns of HIV- infected mothers, 35%. The majority of these individuals remains seronegative on follow-up although a few are PCR+ for HIV DNA. The studies summarized above raised the possibility that cellular immunity, mediated by Type 1 cells, is protective, but humoral immunity, mediated by Type 2 cells is not. If correct, these findings would indicate that AIDS vaccine development should be directed to augment cellular rather than humoral immunity. We have also observed that interleukin-12 (IL-12) strongly enhances the defective in vitro Th responses of HIV+ individuals, including HIV-specific responses. This finding raises the possibility of using IL-12 to enhance cellular immunity in HIV+ patients.